title: Slug promoted vasculogenic mimicry in hepatocellular carcinoma.
abstract: Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumour cells to mimic the pattern of embryonic vasculogenic networks. Epithelial-mesenchymal transition (EMT) regulator slug have been implicated in the tumour invasion and metastasis of human hepatocellular carcinoma (HCC). However, the relationship between slug and VM formation is not clear. In the study, we demonstrated that slug expression was associated with EMT and cancer stem cell (CSCs) phenotype in HCC patients. Importantly, slug showed statistically correlation with VM formation. We consistently demonstrated that an overexpression of slug in HCC cells significantly increased CSCs subpopulation that was obvious by the increased clone forming efficiency in soft agar and by flowcytometry analysis. Meantime, the VM formation and VM mediator overexpression were also induced by slug induction. Finally, slug overexpression lead to the maintenance of CSCs phenotype and VM formation was demonstrated in vivo. Therefore, the results of this study indicate that slug induced the increase and maintenance of CSCs subpopulation and contributed to VM formation eventually. The related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis.
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Sun
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.forename: Tieju
authors.initials: T
authors.lastname: Liu
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.forename: Na
authors.initials: N
authors.lastname: Che
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.forename: Xueyi
authors.initials: X
authors.lastname: Dong
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Jiadong
authors.initials: J
authors.lastname: Chi
authors.forename: Ran
authors.initials: R
authors.lastname: Sun
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000378:metabolism*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010641:Phenotype; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
keywords: Slug; cancer stem cells; hepatocellular carcinoma; vasculogenic mimicry